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- 저자 : Crispino, Caroline (검색결과 2 건)
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Park, Cheon Seok,Kim, Jeong-Yoon,Crispino, Caroline,Chang, Ching Chuan,Ryu, D. Y. 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-
A novel P-type ATPase gene, Saccharomyces cerevisiae PMR1 homologue (YlPMR1), has been cloned and sequenced in the yeast, Yarrowia lipolytica. The putative gene product has 928 amino acids with a calculated molecular mass of 100 050 Da and a p1 of 5.15. The deduced amino-acid sequence analysis demonstrated that the cloned gene product contains all 10 of the conserved regions in P-type ATPases and exhibits 55% amino-acid identity to the S. cerevisiae PMR1 gene product; however, it shows a relatively lower homology to PMCA (24%) and SERCA (33%), confirming the presence of a third class of Ca^2+ -ATPase (secretory pathway Ca^2+ -ATPase, SPCA). The YlPMR1-disrupted strain shows defective growth in low Ca^2+ or EGTA-containing medium. In fact, a longer lag time (60 h) was observed in YlPMR1-defective mutant cells during cultivation in EGTA-containing YPD medium. These growth defects were overcom by adding Ca^2+ and Mn^2+ into the medium. Interestingly, whereas Mn^2+ inhibits growth of the control strain, it significantly improves the growth of YlPMR1-disrupted cells. There results suggest an involvement of the YlPMR1 gene product in Ca^2+ and Mn^2+ ion homeostasis in Y. lipolytica. ⓒ 1997 Elsevier Science B.V.
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Margherita Baldassarri,Chiara Fallerini,Francesco Cetta,Marco Ghisalberti,Cristiana Bellan,Simone Furini,Ottavia Spiga,Sergio Crispino,Giuseppe Gotti,Francesca Ariani,Piero Paladini,Alessandra Renieri 대한암학회 2018 Cancer Research and Treatment Vol.50 No.2
Purpose Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-step whole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients’ peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. Results Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none of which, except one, shared with the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. Conclusion In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.
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